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Volum 10 Numarul 2, 2004

70 Editorial

We are always content to be able to present our readers new and interesting results from the activity of the SRRO members as it is also this issue of the journal that offers several professional novelties, new collaborators as well some general reviews written by most experienced colleagues.

It is a real pleasure to mention first, the paper presented by Ioana Brie and her colleagues about the comet assay as it was implemented in our Research Center for Radiation Oncology, to study the radioinduced lesions of the DNA. For the first time performed in Romania, the authors are presenting also their results and we wish to Ioana, the heart and the driving engine of her group, to complete and translate this experience as soon as possible in the clinical practice also.

Radu Tãnãsescu, presents his results with hyperthermia, a première greeted in due time, several years ago. At present, the method is routinely used in clinic and the author gathered a large experience with diverse combination of hyperthermia and radiation or drugs.

The enlargement of the domains approached by the collaborators of our journal, is seen in the papers presented by Maria Retegan Turdean about the neuroendocrine gastrointestinal tumors, Renata Vasiu with a rare case of an extragstrointestinal stromal tumor or the overview signed by R. Curcã on the current status

of the multimodality treatment in gastric cancer.

The chronicle and the thoughts upon a fine experience that covers a 25 years period, written by Cristina Vitoc, as a memento for the approaching celebration of the 75th anniversary of the foundation of the Cancer Institute Cluj. This round anniversary age is a good moment for thinking and meditate on the beginnings, the importance of the models, formation efforts, an assessment of successes as well of unfulfilled projects but also about the responsibility of the coming generations to continue and to develop the results that have imposed the Institute from Cluj in the Romanian and international oncology.

We are signaling also 2 papers that present a clinical original experience, by Anca Bojan and collaborators on the use of bisphosphonates in the treatment of multiple myeloma and the presence of Diana Osadcii from the Cancer Institute Chişinãu on practical pathological problems in ovarian cancer: we wish her success for the

future and many other presences in the pages of our journal.

In the News, Luciana Pavel brings us information an the activity and the domains of interest for the German Society of Medical Physics from that is to be especially mentioned their program for quality assurance and quality control, program that should be implemented also in Romania. In the same line, another paper of interest is the last version of the assessment and evaluation of the adverse effects of the oncological treatments published by the international professional associations and activated in 2003. The list with the active members of the SRRO closes this issue, like a memento for our annual conference from september in Arad, where we hope to see you again, after a full and well deserved vacation, full of energy for new projects and new achievements!

71 Adverse Effects of Cancer Treatments, CTCAE System v 3.0:Pathology & Evaluation

  1. Ghilezan

Cancer Institute „Prof. I. Chiricuţă” Cluj-Napoca

The increased development of multidisciplinary treatments and the trend for a better overall survival in cancer patients led also to a more awareness for the evaluation and ranking of the adverse treatment effects as a mean for a continuous improvement of the therapeutic ratio. Since 1979 when the first classification has been published, the international professional societies have developed multiple criteria to define and classify these adverse effects, the recent CTCAE v3.0 (http://ctep.info.nih.gov/CTC3/ctc.htm) being implemented routinely in the spring of 2003. The main progress of this version is the use of a unique system for evaluation and classification of the adverse effects of all cancer treatments and an integration of the acute and chronic effects in a model of a same continuous biologic process of the wound healing.

Key words: Adverse effects, Classification.

Radioterapie & Oncologie Medicală, 2004, 2:71-79

80 Neuroendocrine Gastrointestinal Tumours

Maria Retegan Turdean

University District Hospital, Medical Oncology Department, Cluj-Napoca

Neuroendocrine gastrointestinal tumours represent a heterogeneous group of distinct pathological and clinical entities with similar cytochemical and ultrastructural properties.They have the ability to synthesize and secrete peptide hormones and bioactive amines.These products can be identified by immunohistochemical methods and they are frequently released in the circulation and cause the typical hypersecretion-related symptoms and syndromes. Neuroendocrine tumours can be subdivided into two categories with respect to their capacity to release bioactive molecules:functional, hormone-active neuroendocrine tumours and nonfunctional, hormone-inactive neuroendocrine tumours.The progress in diagnosis and treatment of neuroendocrine tumours improved the quality of life and life expentancy, but the outcome with the existing therapy is not satisfactory. It is necessary to develop new therapeutic strategies based on the tumour biology.

Key words: Neuroendocrine tumour, Carcinoid.

Radioterapie & Oncologie Medicală, 2004, 2:80-88

95 In vitro Evaluation of Radiation-induced DNA Damage and Repair Using Comet Assay

Ioana Brie1, Maria Perde2, Eva Fischer2, Piroska Virag2, Olga Soriţãu2, Roxana Ola3, I.D. Postescu2, V. Cernea1,2, N. Ghilezan1 ,2

1UMPh „Iuliu Haţieganu” Cluj-Napoca ;

2Cancer Institute „I. Chiricuţã” Cluj-Napoca;

3”Babeş-Bolyai” University Cluj-Napoca, Dept. of Biology-Geology

Purpose: Pretherapeutic evaluation by Comet Assay of cellular radiosensitivity as an indicator of normal tissue tolerance would enable clinicians to adjust RT to each patient, with consequent improvement in the therapeutic ratio. We report the technique and the preliminary results of a study aiming to develop a predictive assay of normal tissue response to RT.

Material and Method: Lymphocytes from 10 healthy volunteer donors were gamma-irradiated with 2 and 5Gy in vitro and analyzed using the alkaline comet assay performed immediately, at 1h and at 24h after irradiation. Interpretation was done by visual analysis and calculation of two parameters indicating the level of DNA damage in the cells.

Results: A substantial interindividual variability was found, concerning 3 biological parameters of radiosensitivity: radiation-induced DNA damage, capacity of repair and repair kinetics. They made possible the evaluation of the sensitivity to gamma irradiation and of the the repair profile at the individual level.

Conclusions: Comet Assay is a modern, simple, quick and non-expensive method for the study of the cellular radiosensitivity. Ensuring the reproducibility and the sensitivity of this method, it could be a useful predictive assay, enabling radiation doses to be tailored to the individual.

Key words: Comet assay, Lymphocytes, DNA damage, DNA repair, Gamma radiation.

Radioterapie & Oncologie Medicală, 2004, 2:95-104

105 Clinical Results of Antitumoral Hyperthermia in Superficial Recurrences

  1. Tãnãsescu1,2, N. Ghilezan1,2, Cristina Vitoc1, Dana Grecea1, Al. Eniu1

1Cancer Institute„Prof. I. Chiricţã” Cluj-Napoca;

2UMPh „Iuliu Haþieganu“ Cluj-Napoca

We present the Institutes experience referring to the practice of hyperthermia in superficial recurrences of different malignancies. In three years we treated a number of 245 cases, in majority breast cancer (77) followed by head and neck (53) and skin (35). From the beginning, the intention was palliative treatment, the patients had already received standard therapeutic protocols. We used a superficial heating device, made by the Technical University Cluj, based on microwaves emission at 2450 Mhz. Hyperthermia was done alone in 124 cases and in association with external radiotherapy (79) or chemotherapy (18 patients). The best clinical results were obtained in the case of the association hyperthermia-radiotherapy (44% complete and partial response). Hyperthermia proven also to be useful in the reduction of pain and bleeding. The adverse reactions were minimal, with no cases of interruption of treatment. These data represent a rationale for continuing this type of treatment, alone or, when possible, in association with radiochemotherapy.

Key words: Hyperthermia, Therapeutic associations, Superficial recurrences.

Radioterapie & Oncologie Medicală, 2004, 2:105-109

101 The Effects of Bisphosphonates in Multiple Myeloma Patients

Anca Bojan2, Mariana Paţiu1, Anca Vasilache1, Carmen Basarab1, A. Cucuianu2, C. Coldea1, Laura Urian2, Cristiana Fodor1, L. Petrov2

1Cancer Institute „Prof. I. Chiricuţã” Cluj-Napoca;

2UMPh „Iuliu Haþieganu” Cluj-Napoca

Bisphosphonates are a new class of agents that reduce bone complications associated with multiple myeloma. 34patients with multiple myeloma from the Oncological Institute of Cluj Napoca, diagnosed between january 1999 and december 2002 where traeted with bisphosphonates: 18 patients with Clodronate 1600mg/daily and 16 patients with Pamidronate, 90mg/4weeks, for 6 months. All the patients were in stage III, 30 IIIA and 4 IIIB. 18 patients were treated with VMCP and 16 with VCAP. We followed up the intensity of bone pain, hypercalcemia, and the rate of pathological fractures. The results were compared with a group of 34 patients with multiple myeloma treated with chemotherapy alone. The bisphosphonates reduced significantly the bone pain (in 24 of 34 of patients compared with 16 of the34 patients in the group treated with chemotherapy alone), reduce the hypercalcemia (in 12 of the 16 patients treated with bisphisphonates compared with 5 fom the 14 patients treated with chemotherapy alone), but did not significaly influence the rate of pathological fractures.

Key words: Multiple myeloma, Bisfosfonates, Chemotherapy.

Radioterapie & Oncologie Medicală, 2004, 2:110-114

89 25 Years in Managing Breast Cancer

Cristina Vitoc

Cancer Institute „Prof. Ion Chiricuţă”, Cluj-Napoca

In this year 2004, my generation proposes an overview of the management of breast cancer in the last 25 years out of that 75 years since the Cancer Institute „I. Chiricuta” was founded. The report is beginning with the acknowledgment of those who were the pioneers, followed by those who have done the work and for those who already have the responsibility for the future. A short insight in all aspects of the management approach of breast cancer as it was done in the Institute but also extramural, is presented, concerning all activities and goals of our profession: advancing care of the patients, training students and residents, continuous medical education and clinical research. In the end we recognize the leading role of Professor N. Ghilezan and together we are proud to review the advances to which we have contributed, a generous moral legacy for those who are coming to foster an even better future for the Institute and patients.

Key words: Breast Tumor Center , Management, Leadership.

Radioterapie & Oncologie Medicală, 2004, 2:89-94

95 In vitro Evaluation of Radiation-induced DNA Damage and Repair Using Comet Assay

Ioana Brie1, Maria Perde2, Eva Fischer2, Piroska Virag2, Olga Soriţãu2, Roxana Ola3, I.D. Postescu2, V. Cernea1,2, N. Ghilezan1 ,2

1UMPh „Iuliu Haţieganu” Cluj-Napoca ;

2Cancer Institute „I. Chiricuţã” Cluj-Napoca;

3”Babeş-Bolyai” University Cluj-Napoca, Dept. of Biology-Geology

Purpose: Pretherapeutic evaluation by Comet Assay of cellular radiosensitivity as an indicator of normal tissue tolerance would enable clinicians to adjust RT to each patient, with consequent improvement in the therapeutic ratio. We report the technique and the preliminary results of a study aiming to develop a predictive assay of normal tissue response to RT.

Material and Method: Lymphocytes from 10 healthy volunteer donors were gamma-irradiated with 2 and 5Gy in vitro and analyzed using the alkaline comet assay performed immediately, at 1h and at 24h after irradiation. Interpretation was done by visual analysis and calculation of two parameters indicating the level of DNA damage in the cells.

Results: A substantial interindividual variability was found, concerning 3 biological parameters of radiosensitivity: radiation-induced DNA damage, capacity of repair and repair kinetics. They made possible the evaluation of the sensitivity to gamma irradiation and of the the repair profile at the individual level.

Conclusions: Comet Assay is a modern, simple, quick and non-expensive method for the study of the cellular radiosensitivity. Ensuring the reproducibility and the sensitivity of this method, it could be a useful predictive assay, enabling radiation doses to be tailored to the individual.

Key words: Comet assay, Lymphocytes, DNA damage, DNA repair, Gamma radiation.

Radioterapie & Oncologie Medicală, 2004, 2:95-104

105 Clinical Results of Antitumoral Hyperthermia in Superficial Recurrences

  1. Tãnãsescu1,2, N. Ghilezan1,2, Cristina Vitoc1, Dana Grecea1, Al. Eniu1

1Cancer Institute„Prof. I. Chiricţã” Cluj-Napoca;

2UMPh „Iuliu Haþieganu“ Cluj-Napoca

We present the Institutes experience referring to the practice of hyperthermia in superficial recurrences of different malignancies. In three years we treated a number of 245 cases, in majority breast cancer (77) followed by head and neck (53) and skin (35). From the beginning, the intention was palliative treatment, the patients had already received standard therapeutic protocols. We used a superficial heating device, made by the Technical University Cluj, based on microwaves emission at 2450 Mhz. Hyperthermia was done alone in 124 cases and in association with external radiotherapy (79) or chemotherapy (18 patients). The best clinical results were obtained in the case of the association hyperthermia-radiotherapy (44% complete and partial response). Hyperthermia proven also to be useful in the reduction of pain and bleeding. The adverse reactions were minimal, with no cases of interruption of treatment. These data represent a rationale for continuing this type of treatment, alone or, when possible, in association with radiochemotherapy.

Key words: Hyperthermia, Therapeutic associations, Superficial recurrences.

Radioterapie & Oncologie Medicală, 2004, 2:105-109

110 The Effects of Bisphosphonates in Multiple Myeloma Patients

Anca Bojan2, Mariana Paţiu1, Anca Vasilache1, Carmen Basarab1, A. Cucuianu2, C. Coldea1, Laura Urian2, Cristiana Fodor1, L. Petrov2

1Cancer Institute „Prof. I. Chiricuţã” Cluj-Napoca;

2UMPh „Iuliu Haþieganu” Cluj-Napoca

Bisphosphonates are a new class of agents that reduce bone complications associated with multiple myeloma. 34patients with multiple myeloma from the Oncological Institute of Cluj Napoca, diagnosed between january 1999 and december 2002 where traeted with bisphosphonates: 18 patients with Clodronate 1600mg/daily and 16 patients with Pamidronate, 90mg/4weeks, for 6 months. All the patients were in stage III, 30 IIIA and 4 IIIB. 18 patients were treated with VMCP and 16 with VCAP. We followed up the intensity of bone pain, hypercalcemia, and the rate of pathological fractures. The results were compared with a group of 34 patients with multiple myeloma treated with chemotherapy alone. The bisphosphonates reduced significantly the bone pain (in 24 of 34 of patients compared with 16 of the34 patients in the group treated with chemotherapy alone), reduce the hypercalcemia (in 12 of the 16 patients treated with bisphisphonates compared with 5 fom the 14 patients treated with chemotherapy alone), but did not significaly influence the rate of pathological fractures.

Key words: Multiple myeloma, Bisfosfonates, Chemotherapy.

Radioterapie & Oncologie Medicală, 2004, 2:110-114

115 Morphological Aspects of Normal-Size Ovarian Carcinoma

Diana Osadcii

Dept. of Patology, Cancer Institute,2025 Chişinãu, Moldovia Republic

Six cases of ovarian carcinoma with normal-size ovarian were examined hystologically and cytologically. All tumours are bilateral. Five of them had metastatic disease of the peritoneal cavity. Hystology of the carcinoma was that of common epithelial carcinoma of the ovary with variable degrees of differentiation. Morphological features and form-making patterns of cancer cells in primary and metastatic tumours were correlated for cytological and histological investigations. The studies conducted showed the main morphological propries of the primary tumours, retaind in the metastatic tumours. Thus, “normal-sized” ovarian carcinoma has a great tendency to spread externally.

Key words: Cytology, Histology, Serous ovarian tumors.

Radioterapie & Oncologie Medicală, 2004, 2:115-117

118 Extragastrointestinal Stromal Tumor. Clinical Case Report

Renata Vasiu1, Liliana Resiga2, Rodica Nicolau3

1Dept. of Patology UMPh „Iuliu Haţieganu” Cluj;

2Cancer Institute „Ion Chiricuþã” Cluj;

3Dept. of Ginecology, Municipal Hospital Cluj-Napoca

The authors present the case of 63 years old women with an extra-gastrointestinal stromal tumor localized on the colonic serosa and accompanied by small satellite tumors. The macroscopic, microscopic (in optical microscopy with standard, special and immunohistochemically stains) aspects are highlighted with literature revision.

Key words: Extragastrointestinal stromal tumor, Plasmacitoid cells, CD117, CD34.

Radioterapie & Oncologie Medicală, 2004, 2:118-122

123 Multimodality Treatment in Gastric Cancer. Current Status

  1. Curcã

Alba County Hospital, Dept. of Oncology, Alba-Iulia

Gastric cancer is the second commonest cancer worldwide. Surgery is the mainstay of the treatment and, until recently, radiotherapy and chemotherapy were considered to play only a secondary role in the therapeutic armamentarium. Nowadays, new multimodality therapeutical approaches emerged, especially in adjuvant and in neoadjuvant setting. The present paper presents recent advances and controversies regarding the current management of gastric cancer.

Key words: Chemotherapy, Radiotherapy, Gastric cancer.

Radioterapie & Oncologie Medicală, 2004, 2:123-129

130 Present Trends in German Radiology & Radiotherapy

The German Society of Medical Physics, November 11-14, 2003, Heidelberg, Germany

Luciana Pavel

DKFZ, Heidelberg, Germania

The members of the German Society of Medical Physics (DGMP) are organising a meeting once a year, usually during a conference where the latest scientific news are presented in paralell sessions. In 2003, the annual meeting was held in Heidelberg, the beautiful university town on the Neckar, with the following topics: radiotheraapy/clinical dosimetry (positioning,

IMRT) Imaging (functional, molecular & metabolic, morphological), Radioprotection, Hypertermia, Interventional Radiology, Quality Control, etc.An overview of the activities of DGMP is also presented including a study on the present status of the medical physicists in Germany, their training and califications as well an estimation of the future needs.

Key words: Medical physic, Radiotherapy, Professional calification & Perspectives.

Radioterapie & Oncologie Medicală, 2004, 2:130-133

134 MEMBERS OF ROMANIAN SOCIETY OF RADIATION THERAPY AND MEDICAL ONCOLOGY 2004

136 GUIDELINFS FOR AUTHORS